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FLASH GENE

Symbol

TRIM24

contributors: mct/pgu - updated : 28-01-2012

HGNC name	tripartite motif-containing 24
HGNC id	11812

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	7q34      Physical location : 138.145.078 - 138.270.330
Synonym name	hepatoma, PML, RING related protein
	transcriptional intermediary factor 1 alpha
	RING finger protein 82
Synonym symbol(s)	HPRR, TIF1, HTIF1, TIF1A, PTC6, TF1A, RNF82, TIF1ALPHA

DNA

TYPE	functioning gene
STRUCTURE	125.26 kb     20 Exon(s)

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D7S495 - TRIM24 - D7S2560 - TRIM24 - D7S2450 - D7S684 - qter
Authors	UCSC (2009)

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015905 19 splicing 4007 116.7 1050 - 1997 9115274 NM_003852 19 splicing 3905 112.9 1016 - 1997 9115274 using an alternate in-frame splice site compared to variant 1

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver         Lymphoid/Immune thymus         Nervous brain         Reproductive male system prostate       Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Connective bone       Lymphoid

cell lineage	breast cancer cell lineage
cell lines	myeloid lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a RING-zinc finger domain
	two B boxes (one type 1 and one type 2)
	a coiled-coil domain (RBCC), the so-called tripartite motif
	a serine/proline rich region
	a nuclear localization signal (NLS)
	a TIF1 signature sequence (TJS)
	a C-terminal PHD (plant homeodomain)) motif
	a bromodomain (PHD-Bromo domain provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to murine Trim 24 (94.3 pc)
	homolog to rattus Trim24 (91.3 pc)

Homologene

FAMILY

C-VI TRIM family

CATEGORY

regulatory , DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm,nuclear bodies
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	mediating transcriptional control by interaction with the activation function 2 (AF2) region of several nuclear receptors
	potent liver-specific tumor suppressor
	regulates AR-mediated transcription in collaboration with KAT5 and BRD7
	E3-ubiquitin ligase targeting TP53, broadly associated with chromatin silencing, that relies on PHD-Bromo domain and activate oestrogen-dependent genes associated with cellular proliferation and tumour development
	acts as a cell-autonomous tumor suppressor in quiescent hepatocytes
	differentially modulate carcinogenesis in a nuclear receptor and tissue-specific manner
	negative regulator of the interferon/STAT pathway, suggesting that this repression through RARA inhibition may prevent liver cancer

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	cell growth and proliferation
	transcriptional modulator
	myeloid differentiation

PATHWAY

metabolism

signaling

a component	with PML, RXRA, RARA of a transcription complex, retinoic acid dependent
	TRIM24 exists in a major complex with TRIM33 and a lesser abundant complex with TRIM33 and TRIM28

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	silencing domain of KOX1
	interacting with CBX1 and CBX3
	interacting with NR3C2
	partner of TP53 (ubiquitylates and negatively regulates TP53 levels, suggesting TRIM24 as a therapeutic target to restore tumor suppression by TP53)
	binds to BRD7, which can negatively regulate cell proliferation and growth (TRIM24 regulates AR-mediated transcription in collaboration with KAT5 and BRD7)
	interacts with AR and enhances transcriptional activity of AR by dihydrotestosterone in prostate cancer cells
	binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development
	potent co-activator of ESR1, which is associated with cellular proliferation and neoplasia in breast cells
	interacts with the liganded retinoic acid (RA) receptor to repress its transcriptional activity
	cooperative action of TRIM24 and TRIM33 in tumor suppression
	is a novel negative regulator of the IFN/STAT pathway, suggesting that this repression through RARA inhibition may prevent liver cancer

cell & other

REGULATION

Other	target of PML
	phosphorylated upon DNA damage, probably by ATM or ATR
	modified by SUMO-1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   translocation     5'- TRIM24 - RET -3' fused in papillary thyroid carcinoma (see PTC6) tumoral fusion       with FGFR1 in t(7;8) (q34; p11) in myeloproliferative syndrome tumoral     --other   aberrant expression negatively correlates with survival of breast cancer patients ( tumoral       loss of function results in the development of hepatocellular carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer     dual domain histone reader with considerable potential as a therapeutic target in multiple cancers cancer     therapeutic targeting of TRIM24 protein to increase TP53 protein levels may offer an avenue toward restoration of TP53-functions and induced apoptosis of tumor cells

ANIMAL & CELL MODELS

inhibition of retinoic acid signaling markedly reduces hepatocyte proliferation in Trim24 -/- mice